Plos One
-
Prospective syndromic surveillance of emergency department visits has been used for near-real time tracking of communicable diseases to detect outbreaks or other unexpected disease clusters. The utility of syndromic surveillance for tracking cardiovascular events, which may be influenced by environmental factors and influenza, has not been evaluated. We developed and evaluated a method for tracking cardiovascular events using emergency department free-text chief complaints. ⋯ Near real-time emergency department chief complaint data may be useful for timely surveillance of cardiovascular morbidity related to ambient air pollution and other environmental events.
-
Since the early 2000s, aid organizations and developing country governments have invested heavily in AIDS treatment. By 2010, more than five million people began receiving antiretroviral therapy (ART)--yet each year, 2.7 million people are becoming newly infected and another two million are dying without ever having received treatment. As the need for treatment grows without commensurate increase in the amount of available resources, it is critical to assess the health and economic gains being realized from increasingly large investments in ART. ⋯ This investment is expected to save 18.5 million life-years and return $12 to $34 billion through increased labor productivity, averted orphan care, and deferred medical treatment for opportunistic infections and end-of-life care. Under alternative assumptions regarding the labor productivity effects of HIV infection, AIDS disease, and ART, the monetary benefits range from 81 percent to 287 percent of program costs over the same period. These results suggest that, in addition to the large health gains generated, the economic benefits of treatment will substantially offset, and likely exceed, program costs within 10 years of investment.
-
Development of Type 2 diabetes, like obesity, is promoted by a genetic predisposition. Although several genetic variants have been identified they only account for a small proportion of risk. We have asked if genetic risk is associated with abnormalities in storing excess lipids in the abdominal subcutaneous adipose tissue. ⋯ Genetic predisposition for Type 2 diabetes, but not obesity, is associated with an impaired ability to recruit new adipose cells to store excess lipids in the subcutaneous adipose tissue, thereby promoting ectopic lipid deposition. This becomes particularly evident in non-obese individuals since obesity per se promotes a dysmetabolic state irrespective of genetic predisposition. These results identify a novel susceptibility factor making individuals with a genetic predisposition for Type 2 diabetes particularly sensitive to the environment and caloric excess.
-
Exon 11 of the insulin receptor gene (INSR) is alternatively spliced in a developmentally and tissue-specific manner. Linker scanning mutations in a 5' GA-rich enhancer in intron 10 identified AGGGA sequences that are important for enhancer function. Using RNA-affinity purification and mass spectrometry, we identified hnRNP F and hnRNP A1 binding to these AGGGA sites and also to similar motifs at the 3' end of the intron. ⋯ The SR protein SRSF1 (SF2/ASF) co-purified on the GA-rich enhancer and, interestingly, also competes with hnRNP A1 for binding to the splice site. A point mutation -3U→C decreases hnRNP A1 binding, increases SRSF1 binding and renders the exon constitutive. Lastly, our data point to a functional interaction between hnRNP F and SRSF1 as a mutant that eliminates SRSF1 binding to exon 11, or a SRSF1 knockdown, which prevents the stimulatory effect of hnRNP F over expression.
-
Yellow fever vaccination (YF-17D) can cause serious adverse events (SAEs). The mechanism of these SAEs is poorly understood. Older age has been identified as a risk factor. We tested the hypothesis that the humoral immune response to yellow fever vaccine develops more slowly in elderly than in younger subjects. ⋯ We found that elderly subjects had a delayed antibody response and higher viraemia levels after yellow fever primovaccination. We postulate that with older age, a weaker immune response to yellow fever vaccine allows the attenuated virus to cause higher viraemia levels which may increase the risk of developing SAEs. This may be one piece in the puzzle of the pathophysiology of YEL-AVD.